Trifluoroacetic acid → 1-(7-bromo-4-methoxy-1H-pyrrolo[2,3-c]pyridin-3-yl)-2-(4-(pyridin-2-yl)-5,6-dihydropyrido[3,4-d]pyrimidin-7(8H)-yl)ethane-1,2-dione

HRID 885058Notes

Reaction equation

HRID 885058 reaction equation
[Br:1][C:2]1[N:3]=[CH:4][C:5]([O:16][CH3:17])=[C:6]2[C:10]([C:11](=[O:15])[C:12]([OH:14])=O)=[CH:9][NH:8][C:7]=12.[N:18]1[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=1[C:24]1[C:25]2[CH2:33][CH2:32][NH:31][CH2:30][C:26]=2[N:27]=[CH:28][N:29]=1.C(O)(C(F)(F)F)=O.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F>CN(C=O)C>[Br:1][C:2]1[N:3]=[CH:4][C:5]([O:16][CH3:17])=[C:6]2[C:10]([C:11](=[O:15])[C:12]([N:31]3[CH2:32][CH2:33][C:25]4[C:24]([C:19]5[CH:20]=[CH:21][CH:22]=[CH:23][N:18]=5)=[N:29][CH:28]=[N:27][C:26]=4[CH2:30]3)=[O:14])=[CH:9][NH:8][C:7]=12

Participants

7

Reactant 5

HCID 6422Trifluoroacetic acidHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 575904977-Bromo-4-methoxy-α-oxo-1H-pyrrolo[2,3-c]pyridine-3-acetic acidHCID 580260644-(Pyridin-2-yl)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidine

Product 1

HCID 580260381-(7-bromo-4-methoxy-1H-pyrrolo[2,3-c]pyridin-3-yl)-2-(4-(pyridin-2-yl)-5,6-dihydropyrido[3,4-d]pyrimidin-7(8H)-yl)ethane-1,2-dioneYield 76%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a flask containing 2-(7-bromo-4-methoxy-1H-pyrrolo[2,3-c]pyridin-3-yl)-2-oxoacetic acid (0.264 g, 0.884 mmol) was added a solution of 4-(pyridin-2-yl)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidine, TFA (0.5 g, 1.149 mmol) in DMF (8 mL) followed by Hunig's Base (0.772 mL, 4.42 mmol) and finally TBTU (0.369 g, 1.149 mmol). After stirring the mixture at rt for 4 h, it was quenched with 10 mL of water and concentrated under reduced pressure. The residue was diluted with water (25 mL) and sat. aq. ammonium chloride (25 mL) added to the mixture. The mixture was extracted with dichloromethane (3×40 mL). The combined organic layers were washed with sat. aq. NaHCO3, dried with MgSO4, filtered and concentrated under reduced pressure. The residue was purified by BIOTAGE® flash chromatography using a 0-6% MeOH in dichloromethane gradient. The expected product, 1-(7-bromo-4-methoxy-1H-pyrrolo[2,3-c]pyridin-3-yl)-2-(4-(pyridin-2-yl)-5,6-dihydropyrido[3,4-d]pyrimidin-7(8H)-yl)ethane-1,2-dione (0.333 g, 0.675 mmol, 76% yield), was isolated as a brown solid. LC/MS: m/z 493 (M+H)+, 495.13 (M+3H)+, 2.177 min (method 3). 1H NMR (500 MHz, DMSO-d6) δ ppm 13.11 (br. s., 1H) 9.05-9.19 (m, 1H) 8.66-8.78 (m, 1H) 8.33-8.44 (m, 1H) 7.99-8.12 (m, 2H) 7.82 (s, 1H) 7.50-7.60 (m, 1H) 4.66-4.91 (m, 2H) 3.63-3.92 (m, 5H) 3.11-3.32 (m, 2H).

Workup

  1. customit was quenched with 10 mL of water
  2. concentrationconcentrated under reduced pressure
  3. additionThe residue was diluted with water (25 mL) and sat. aq. ammonium chloride (25 mL)
  4. additionadded to the mixture
  5. extractionThe mixture was extracted with dichloromethane (3×40 mL)
  6. washThe combined organic layers were washed with sat. aq. NaHCO3
  7. dry with materialdried with MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified by BIOTAGE® flash chromatography

Sources & evidence

ORD record
ord-74068e7527bd46b6853193579b41882c
Source dataset
uspto-grants-2012_08
Patent number
US08242124B2

Reaction notes

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